Anticalculus oral composition

ABSTRACT

In an anticalculus oral composition containing in an orally acceptable vehicle one or a mixture of water soluble linear molecularly dehydrated alkali metal or ammonium polyphosphate salts as essential anticalculus agent, an amount of a fluoride ion source sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions, and one or a mixture of water soluble alkali metal or ammonium synthetic anionic polymeric polycarboxlate salts, the improvement comprising employing in said composition a polyphosphate ion:polycarboxylate salt weight ratio ranging from about 0.3:1 to about 2.5:1.

This application is a continuation-in-part of application Ser. No.842,101, filed Mar. 20, 1986, now U.S. Pat. No. 4,806,340 which is inturn a continuation-in-part of application Ser. No. 775,851, now U.S.Pat. No. 4,627,977.

This invention relates to oral compositions containing an anticalculusagent.

Calculus is a hard, mineralized formation which forms on the teeth.Regular brushing aids in preventing a rapid build-up of these deposits,but even regular brushing is not sufficient to remove all of thecalculus deposits which adhere to the teeth. Calculus is formed on theteeth when crystals of calcium phosphates begin to be deposited in thepellicle and extracellular matrix of the dental plaque and becomesufficiently closely packed together for the aggregates to becomeresistant to deformation. There is no complete agreement on the route bywhich calcium and orthophosphate ultimately become the crystallinematerial called hydroxyapatite (HAP). It is generally agreed, however,that at higher saturations, that is, above the critical saturationlimit, the precursor to crystalline HAP is an amorphous ormicrocrystalline calcium phosphate. "Amorphous calcium phosphate"although related to hydroxyapatite differs from it in atomic structure,particle morphology, and stoichiometry. The X-ray diffraction pattern ofamorphous calcium phosphate shows broad peaks typical of amorphousmaterials, which lack the long-range atomic order characteristic of allcrystalline materials, including HAP. It is apparent therefore thatagents which effectively interfere with crystalline growth of HAP willbe effective as anticalculus agents. A suggested mechanism by which theanticalculus agents of this invention inhibit calculus formationprobably involves an increase of the activation energy barrier thusinhibiting the transformation of precursor amorphous calcium phosphateto HAP.

Studies have shown that there is a good correlation between the abilityof a compound to prevent HAP crystalline growth in vitro and its abilityto prevent calcification in vivo, provided of course that such compoundis stable in an inert to saliva and its components.

It is well known in the art that water soluble hexametaphosphates,tripolyphosphates and pyrophosphates and the like are effective calciumand magnesium ion suppressors, inhibitors, sequestrants and/or chelatingagents, and are effective inhibitors of HAP formation in vitro. U.S.Pat. No. 4,515,772 issued May 7, 1985 to Parran et al discloses andclaims oral anticalculus compositions containing a fluoride ion sourceand soluble dialkali metal pyrophosphates alone or admixed withtetraalkali metal pyrophosphates. The voluminous number of acknowledgedprior art and "References Cited" in this patent indicate the many usesand functions of these polyphosphates hitherto proposed in oralcompositions.

However, as in part admitted in the aforesaid patent disclosure and asshown in the above-mentioned parent patent applications, these linearmolecularly dehydrated polyphosphates (i.e. hexametaphosphate,tripolyphosphates, pyrophosphates, etc.) in common, when introduced intothe oral cavity and/or saliva are significantly hydrolyzed by salivaryenzymes (phosphatases) to orthophosphates which are ineffective asinhibitors of HAP formation.

The aforesaid U.S. Pat. No. 4,627,977, the disclosure of which isincorporated herein, discloses oral compositions containingpolyphosphate as anticalculus agent and a combination of fluoride andpolymeric polycarboxylate to inhibit the enzymatic hydrolysis of thepolyphosphate in saliva. The aforesaid application Ser. No. 842,101, thedisclosure of which is also incorporated herein, discloses dentifricesof similar composition containing as polyphosphate at least about 4.3%tetrapotassium pyrophosphate and up to about 2.7% tetrasodiumpyrophosphate, thus eliminating the problem of grittiness whenincorporating more than about 2.7-3% of the relatively insolubletetrasodium salt.

Problems still exist concerning these compositions in the form ofobjectionable taste tendencies of the tetrapotassium salts and thetendency towards decreased anticaries effects of the fluoride withincreasing amounts of polyphosphate ion.

It is an object of this invention to provide an improved anticalculusoral composition which will not be subject to one or more of the aboveproblems and disadvantages.

A further object of this invention is the provision of such acomposition containing relatively lower proportions of polyphosphateion, especially pyrophosphate ion, and/or lower to zero proportions ofpotassium polyphosphates, especially tetrapotassium pyrophosphate.

A still further object of the invention is to provide an oralcomposition which inhibits the transformation of amorphous calciumphosphate to HAP crystal structure normally associated with calculus andis effective over a relatively wide pH range and/or with improvedcosmetic properties.

Another object of this invention is the provision of an improved methodfor inhibiting the formation of calculus.

Other objects and advantages will appear as the description proceeds.

In accordance with certain of its aspects, the invention relates to anoral composition containing in an orally acceptable vehicle,approximately by weight, an effective anticalculus amount in the rangeof 0.1 to 7%, preferably to below 3%, more preferably to 1.3%, stillmore preferably 0.5 to 1.3%, of one or a mixture of water soluble linearmolecularly dehydrated alkali metal or ammonium polyphosphate,especially pyrophosphate, salts as essential anticalculus agent, anamount of a fluoride ion source sufficient to supply 25 ppm to 2,000 ppmof fluoride ions, and one or a mixture of water soluble alkali metal orammonium synthetic anionic polymeric polycarboxylate salts having amolecular weight of about 1,000 to about 1,000,000, the polyphosphateion:polycarboxylate salt weight ratio ranging from about 0.3:1 to about2.5:1, preferably about 0.5:1 to about 2:1, more preferably about 0.8:1to about 1.2:1.

It has been found that use of the aforementioned polyphosphateion:polycarboxylate salt ratios, especially pyrophosphateion:polycarboxylate salt ratios, unexpectedly enables the attainment ofthe above-mentioned objects of this invention. Concentrations ofpolyphosphate ion, especially pyrophosphate ion, may be thereby loweredto below about 3 wt.%, even below about 1.5 wt.%, e.g. in a range ofabout 0.1 to about 1.3 wt.%, preferably about 0.5 to about 1.3 wt.%. Thesodium polyphosphate salts, especially tetrasodium pyrophosphate, may beemployed within these ranges without giving rise to the problem ofgrittiness or the need for the alternative of employing the more solublepotassium salts, which are more expensive and tend to introduce tasteproblems, especially tetrapotassium pyrophosphate. Anticalculus resultsof use of composition containing the aforementioned polyphosphateion:polycarboxylate salt ratios are unexpectedly usually as good as andoften better than compositions containing other ratios.

Synthetic anionic polymeric polycarboxylates and their complexes withvarious cationic germicides, zinc and magnesium have been previouslydisclosed as anticalculus agents per se in, for example U.S. Pat. No.3,429,963 to Shedlovsky and instant assignee, U.S. Pat. No. 4,152,420 toGaffar and instant assignee, U.S. Pat. No. 3,956,480 to Dichter et al.and instant assignee, U.S. Pat. No. 4,138,477 to Gaffar and instantassignee, and U.S. Pat. No. 4,183,914 to Gaffar et al. It is to beunderstood that the synthetic anionic polymeric polycarboxylates sodisclosed in these patents are operative in the compositions and methodsof this invention and such disclosures are to that extent incorporatedherein by reference thereto.

The synthetic anionic polymeric polycarboxylates employed herein are, asindicated above, well known, being often employed in the form of theirfree acids or preferably partially or more preferably fully neutralizedwater soluble alkali metal (e.g. potassium and preferably sodium) orammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydrideor acid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether (methoxyethylene), having a molecularweight (M.W.) of about 30,000 to about 1,000,000, preferably to about500,000, more preferably to about 250,000. These copolymers areavailable for example as Gantrez AN 139 (M.W. 500,000), A.N. 119 (M.W.250,000) and preferably S-97 Pharmaceutically (M.W. 70,000), of GAFCorporation. The term "synthetic" is intended to exclude knownthickening or gelling agents comprising carboxymethylcellulose and otherderivatives of cellulose and natural gums.

Other operative polymeric polycarboxylates include those disclosed inU.S. Pat. No. 3,956,180 referred to above such as the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrrolidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000, and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred U.S. Pat. No. 4,138,477 and 4,183,914 include copolymers ofmaleic anhydride with styrene, isobutylene or ethyl vinyl ether,polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylicoligomers of M.W. as low as 1,000, available as Uniroyal ND-2.

Suitable generally are polymerized olefinically or ethylenicallyunsaturated carboxylic acid containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrilacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alphaphenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility.

Also useful herein are so-called carboxyvinyl polymers, disclosed astoothpaste components in U.S. Pat. No. 3,980,767 issued Sept. 14, 1976to Choun et al, U.S. Pat. No. 3,935,306 issued Jan. 27, 1976 to Robertset al, U.S. Pat. No. 3,919,409 issued Nov. 11, 1975 to Perla et al, U.S.Pat. No. 3,911,904 issued Oct. 7, 1975 to Harrison, and U.S. Pat. No.3,711,604 issued Jan. 16, 1973 to Colodney et al. They are commerciallyavailable for example under the trademarks Carbopol 934, 940 and 941 ofB. F. Goodrich, these products consisting essentially of a colloidallywater-soluble polymer of polyacrylic acid crosslinked with from about0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol ascross-linking agent.

The synthetic anionic polymeric polycarboxylate component is mainly ahydrocarbon with optional halogen and O-containing substituents andlinkages as present in for example ester, ether and OH groups, and whenpresent is generally employed in the instant composition in approximateweight amounts of 0.05 to 5%, preferably 0.05 to 4%, more preferably 0.1to 3%. Amounts in the upper portions of these ranges are typicallyemployed in dentifrice compositions containing a dental abrasive andused in conjunction wih brushing of the teeth, e.g. tooth pastes(including creams), gels, powders and tablets. Amounts in excess ofthese ranges may be employed for thickening or gelling purposes.

The sources of fluoride ion, or fluoride-providing compounds, requiredaccording to this invention as an essential acid phosphatase andpyrophosphatase enzyme inhibitor component, are well known in the art asanti-caries agents and also act as such agents in the practice of thisinvention. These compounds may be slightly soluble in water or may befully water-soluble. They are characterized by their ability to releasefluoride ions in water and by freedom from undesired reaction with othercompounds of the oral preparation. Among these materials are inorganicfluoride salts, such as soluble alkali metal, alkaline earth metalsalts, for example, sodium fluoride, potassium fluoride, ammoniumfluoride, calcium fluoride, a copper fluoride such as cuprous fluoride,zinc fluoride, barium fluoride, sodium fluorosilicate, ammoniumfluorosilicate, sodium fluorozirconate, sodium monofluorophosphate,aluminum mono- or di-fluorophosphate, and fluorinated sodium calciumpyrophosphate. Alkali metal and tin fluorides such as sodium andstannous fluorides sodium monofluorophosphate (MFP) and mixturesthereof, are preferred.

The amount of fluoride-providing compound is dependent to some extentupon the type of compound, its solubility, and the type of oralpreparation, but it must be a nontoxic amount, generally about 0.005 toabout 3.0% in the preparation. In a dentifrice preparation, e.g. dentalgel, toothpaste (including cream), toothpowder, or dental tablet, anamount of such compound which releases up to about 5,000 ppm of F ion byweight of the preparation is considered satisfactory. Any suitableminimum amount of such compound may be used, but it is preferable toemploy sufficient compound to release abut 300 to 2,000 ppm, morepreferably about 800 to about 1,500 ppm of fluoride ion. Typically, inthe cases of alkali metal fluorides and stannous fluoride, this compoundis present in an amount up to about 2% by weight, based on the weight ofthe preparation, and preferably in the range of about 0.05% to 1%. Inthe case of sodium monofluorophosphate, the compound may be present inan amount of about 0.1-3%, more typically about 0.76%.

In oral preparations such as mouthwash, lozenges and chewing gum, thefluoride-providing compound is typically present in an amount sufficientto release up to about 500 ppm, preferably about 25 to about 300 ppm byweight of fluoride ion. Generally about 0.005 to about 1.0 wt.% of suchcompound is present.

In certain highly preferred forms of the invention the oral compositionmay be substantially liquid in character, such as a mouthwash or rinse.In such a preparation the vehicle is typically a water-alcohol mixturedesirably including a humectant as described below. Generally, theweight ratio of water to alcohol is in the range of from about 1:1 toabout 20:1, preferably about 3:1 to 10:1 and more preferably about 4:1to about 6:1. The total amount of water-alcohol mixture in this type ofpreparation is typically in the range of from about 70% to about 99.9%by weight of the preparation.

The pH of such liquid and other preparations of the invention isgenerally in the range of from about 4.5 to about 10 and typically fromabout 5.5 to 9. The pH is preferably in the range of from about 6 toabout 8.0. It is noteworthy that the compositions of the invention maybe applied orally at a pH below 5 without substantially decalcifying orotherwise damaging dental enamel. The pH can be controlled with acid(e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) orbuffered (as with sodium citrate, benzoate, carbonate, or bicarbonate,disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In certain other desirable forms of this invention, the oral compositionmay be substantially solid or pasty in character, such as toothpowder, adental tablet, a toothpaste, gel or dental cream. The vehicle of suchsolid or pasty oral preparations generally contains polishing material.Examples of polishing materials are water-insoluble sodiummetaphosphate, potassium metaphosphate tricalcium phosphate, dihydratedcalcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate,magnesium, orthophosphate, trimagnesium phosphate, calcium carbonate,aluminum silicate, zirconium silicate, silica, bentonite, and mixturesthereof. Other suitable polishing materials include the particulatethermosetting resins described in U.S. Pat. No. 3,070,510 of Dec. 15,1962 such as melamine-, phenolic-, and urea-formaldehydes, andcross-linked polyepoxides and polyesters. Preferred polishing materialsinclude crystalline silica having particle sizes of up to about 5microns, a mean particle size of up to about 1.1 microns, and a surfacearea of up to about 50,000 cm.² /gm., silica gel or colloidal silica,and complex amorphous alkali metal aluminosilicate.

When visually clear gels are employed, a polishing agent of colloidalsilica, such as those sold under the trademark SANTOCEL as Santocel 100and alkali metal alumino-silicate complexes are particularly useful,since they have refractive indices close to the refractive indices ofgelling agent-liquid (including water and/or humectant) systems commonlyused in dentifrices.

Many of the so-called "water-insoluble" polishing materials are anionicin character and also included small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any suitable manner asillustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4thEdition, pp. 510-511. The forms of insoluble sodium metaphosphate knownas Madrell's salt and Kurrol's salt are further examples of suitablematerials. These metaphosphate salts exhibit only a minute solubility inwater, and therefore are commonly referred to as insolublemetaphosphates (IMP). There is present therein a minor amount of solublephosphate material as impurities, usually a few percent such as up to 4%by weight. The amount of soluble phosphate material, which is believedto include a soluble sodium trimetaphosphate in the case of insolublemetaphosphate, should be reduced or eliminated as by washing with water.The insoluble alkali metal metaphosphate is typically employed in powderform of a particle size such that no more than about 1% of the materialis larger than about 37 microns.

The polishing material is generally present in the solid or pastycompositions in weight concentrations of about 10% to about 99%.Preferably, it is present in amounts ranging from about 10% to about 75%in toothpaste, and from about 70% to about 99% in toothpowder.

In a toothpaste, the liquid vehicle may comprise water and humectanttypically in an amount ranging from about 10% to about 90% by weight ofthe preparation. Glycerine, propylene glycol, sorbitol, polypropyleneglycol and/or polyethylene glycol (e.g. 400-600) exemplify suitablehumectants/carriers. Also advantageous are liquid mixtures of water,glycerine and sorbitol. In clear gels where the refractive index is animportant consideration, about 3-30 wt.% of water, 0 to about 80 wt.% ofglycerine, and about 20-80 wt.% of sorbitol is preferably employed.

Toothpastes, creams and gels typically contain a natural or syntheticthickener or gelling agent in proportions of about 0.1 to about 10,preferably about 0.5 to about 5, wt.%. A suitable thickener is synthetichectorite, a synthetic colloidal magnesium alkali metal silicate complexclay available for example as Laponite (e.g. CP, P 2002, D) marketed byLaporte Industries Limited. Laponite D analysis shows, approximately byweight, 58.00% SiO₂, 25.40% MgO, 3.05% Na₂ O, 0.98% Li₂ O, and somewater and trace metals. Its true specific gravity is 2.53 and it has anapparent bulk density (g./ml. at 8% moisture) of 1.0.

Other suitable thickeners include Irish moss, gum tragacanth, starch,polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g.available as Natrosol), sodium carboxymethyl cellulose, and colloidalsilica such as finely ground Syloid (e.g. 244).

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitable labelled packages.Thus a jar of mouthrinse will have a label describing it, in substance,as a mouthrinse or mouthwash and having directions for its use; and atoothpaste, cream or gel will usually be in a collapsible tube,typically aluminum, lined lead or plastic, or other squeeze, pump orpressurized dispenser for metering out the contents, having a labeldescribing it, in substance, as a toothpaste, gel or dental cream.

Organic surface-active agents are used in the compositions of thepresent invention to achieve increased prophylactic action, assist inachieving thorough and complete dispersion of the anticalculus agentthroughout the oral cavity, and render the instant compositions morecosmetically acceptable. The organic surface-active material ispreferably anionic, nonionic or ampholytic in nature, and it ispreferred to employ as the surface-active agent a detersive materialwhich imparts to the composition detersive and foaming properties.Suitable examples of anionic surfactants are watersoluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglyceride of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2 dihydroxy propanesulfonate, and the substantially saturated higher aliphatic acyl amidesof lower aliphatic amino carboxylic acid compounds, such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and thelike. Examples of the last mentioned amides are N-lauroyl sarcosine, andthe sodium potassium, and ethanolamine salts of N-lauroyl, N-myristoyl,or N-palmitoyl sarcosine which should be substantially free from soap orsimilar higher fatty acid material. The use of these sarcosinatecompounds in the oral compositions of the present invention isparticularly advantageous since these materials exhibit a prolonged andmarked effect in the inhibition of acid formation in the oral cavity dueto carbohydrate breakdown in addition to exerting some reduction in thesolubility of tooth enamel in acid solutions.

Examples of water-soluble nonionic surfactants are condensation productsof ethylene oxide with various reactive hydrogen-containing compoundreactive therewith having long hydrophobic chains (e.g. aliphatic chainsof about 12 to 20 carbon atoms), which condensation products("ethoxamers") contain hydrophilic polyoxyethylene moieties, such ascondensation products of poly(ethylene oxide) with fatty acids, fattyalcohols, fatty amides, polyhydric alcohols (.e.g sorbitan monostearate)and polypropyleneoxide (e.g. Pluronic materials).

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds, other anticalculus agents, and/or ammoniatedmaterial such as urea, diammonium phosphate, and mixtures thereof. Theseadjuvants, where present, are incorporated in the preparations inamounts which do not substantially adversely affect the properties andcharacteristics desired.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, peppermint, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, sorbitol, xylitol, sodium cyclamate, perillartine, APM(aspartyl phenylalanine methyl ester), saccharine and the like.Suitably, flavor and sweetening agents may together comprise from about0.1% to 5% more of the preparation.

In the preferred practice of this invention an oral compositionaccording to this invention such as a mouthwash or dentifrice is appliedregularly to the oral cavity as by "swishing" or brushing dentalsurfaces, such as every second or third day or preferably from 1 to 3times daily, at a pH of about 4.5 to about 10, generally about 5.5 toabout 9, preferably about 6 to 8, for at least 2 weeks up to 8 weeks ormore up to lifetime. The composition is typically removed by rinsingwith water after each application.

The compositions of this invention can be incorporated in lozenges, orin chewing gum or other products, e.g. by stirring into a warm gum baseor coating the outer surface of a gum base, illustrative of which may bementioned jelutone, rubber latex, vinylite resins, etc., desirably withconventional plasticizers or softeners, sugar or other sweeteners orcarbohydrates such as glucose, sorbitol and the like.

The vehicle or carrier in a tablet or lozenge is a non-cariogenic solidwater soluble soluble polyhydric alcohol (polyol) such as mannitol,xylitol, sorbitol, maltitol, a hydrogenated starch hydrolysate, Lycasin,hydrogenated glucose, hydrogenated disaccharides, and hydrogenatedpolysaccharides, in an amount of about 90-98% by weight of the totalcomposition. Solid salt such as sodium bicarbonate, sodium chloride,potassium bicarbonate or potassum chloride may totally or partiallyreplace the polyol carrier.

Tableting lubricants, in minor amounts of about 0.1 to 5% by weight, maybe incorporated into the tablet or lozenge formulation to facilitate thepreparation of both the tablets and lozenges. Suitable lubricantsinclude vegetable oils such as coconut oil, magnesium stearate, aluminumstearate, talc, starch and carbowax.

Lozenge formulations contain about 2% gum as barrier agent to provide ashiny surface as opposed to a tablet which has a smooth finish. Suitablenon-cariogenic gums include Kappa carrageenan, carboxymethyl cellulose,hydroxyethyl cellulose, Gantrez, and the like.

The lozenge or tablet may optionally be coated with a coating materialsuch as waxes, shellac, carboxymethyl cellulose, polyethylene/maleicanhydride copolymer or Kappa-carrageenan to further increase the time ittakes the tablet or lozenge to dissolve in the mouth. The uncoatedtablet or lozenge is slow dissolving, providing a sustained release rateof active ingredients of about 3 to 5 minutes. Accordingly, the soliddose tablet and lozenge composition of this invention affords arelatively longer time period of contact of the teeth in the oral cavitywith the active ingredients.

The following examples are further illustrative of the nature of thepresent invention, but it is understood that the invention is notlimited thereto. All amounts and proportions referred to herein and inthe appended claims are by weight and temperatures are in degrees C.unless otherwise indicated.

EXAMPLE 1 IN VITRO INHIBITION OF HAP FORMATION

The in vitro formation of HAP is measured titrimetrically via a pH statprocedure. Stock solutions of 0.1M CaCl₂ and 0.1M NaH₂ PO₄ are preparedfresh in CO₂ -free deionized distilled water. To 23 ml. CO₂ -freedeionized distilled water 1.0 ml. of the stock phosphate solution andindependently 1.0 ml. of aqueous solutions containing concentrations ofcomponents listed in Table 1 below of the anticalculus composition beingtested are added followed by 1.0 ml. of the stock calcium chloridesolution which initiates the reaction. The reaction is conducted at 25°C. and pH 7.4 under a nitrogen atmosphere. Consumption of 0.1N NaOH isrecorded automatically from which the time required for crystalformation is determined. TABLE 1 shows the results of this procedure.

                  TABLE 1                                                         ______________________________________                                                                             Time(min.)                                                                    of HAP                                   Pyrophosphate.sup.1                                                                     Gantrez.sup.2                                                                          Pyro/Gantrez                                                                              NaF   Crystal                                  Anion (ppm)                                                                             (ppm.)   Wt./Ratio   (ppm) Formation                                ______________________________________                                        0         0        --          --    19                                       (water control)                                                               0         20       --          --    20                                       10        0        --          --    31.5                                     10        5        2:1         --    32                                       10        10       1:1         --    32.5                                     10        20       0.5:1       --    40                                       20        0        --          --    33.0                                     20        5        4:1         --    37.5                                     20        10       2:1         --    59.5                                     20        20       1:1         --    65.9                                     20        22       0.9:1       --    66.0                                     20        20       1:1         1.7   66.0                                     20        40       0.5:1       --    50.2                                     20        40       0.5:1       1.7   51.5                                     ______________________________________                                    

TABLE 1 shows that at the threshold level of 20 ppm, the delay in HAPformation is 14.0 minutes (33-19) with pyrophosphate anion alone, andwith Gantrez alone is essentially non-existent (20-19). However, thecombination of 20 ppm pyrophosphate anion and 20 ppm Gantrezunexpectedly yields a prolonged delay of about 47 minutes (65.9-19),indicating synergism.

The validity of the use of the 20 ppm level is based on the separationof chelation vs. crystal growth inhibition. In the above test, thecrystal growth inhibition occurs at a substoichiometric ratio (calciumin the system is 160 ppm vs. the 20 ppm pyro, a ratio of 8:1 indicatingit is not merely a chelation effect).

As shown in the following TABLE A based on previous studies, 18.8 mg. ofpyrophosphate anion is retained in the mouth from 2% tetrasodiumpyrophosphate (1.3% pyrophosphate anion) which is equivalent to 18,000ppm of pyro.

                  TABLE A                                                         ______________________________________                                        PYROPHOSPHATE ION ORAL                                                        RETENTION STUDIES (SOLUTION)                                                  Original  Amount of               Average                                     Tetrasodium                                                                             Pyro-      Amount of    Pyro-                                       Pyrophosphate                                                                           phosphate  Pyrophosphate                                                                              phosphate                                   in solution                                                                             delivered  retained     retained                                    (%)       (mg)       (mg)         (mg)                                        ______________________________________                                         3.3       499.5      62.4                                                                                        60.5                                      3.3       504.0      58.6                                                      2.0       293.6      17.0                                                                                        18.8                                      2.0       297.5      20.6                                                      0.5       76.7       19.9                                                                                        20.2                                      0.5       76.1       20.5                                                     ______________________________________                                    

Humans normally secrete about 1 to 1.5 liters of saliva per day.Therefore the equivalent concentration is 18,800/1,000 or 18.8 ppm perunit time in the mouth. This is the rationale for the 20 ppm level fordetermining the continuous threshold effect for HAP inhibition.

EXAMPLE 2 IN VIVO CALCULUS INHIBITION

Twenty-one day old male weanling Sprague-Dawley rats were randomizedinto 12 animals per group. The animals were fed a calculogenic diet(RC-16') and deionized water, ad libitum. At the beginning of the study,all animal were inoculated with a suspension of S. mutans (67615) and A.viscosus (OMZ-105-N14) to stimulate plaque and calculus formation.

Each rat was treated once daily (except Saturday and Sunday) with 0.2ml. of test solution delivered intraorally with an automatic pipettor.All animals were sacrificed after three weeks of treatment and the jawswere stripped of flesh and prepared for calculus scoring.

Calculus on both maxillary and mandibular quadrants was evaluated usingthe calculus surface severity index method of Briner and Francis¹. Theresults of the study are listed in TABLE 2. The "Gantrez" in the testsolutions was S97, as in EXAMPLE 1. The pyrophosphate ion ("Pyro") inthe test solutions was derived from a 3:1 mixture of tetrapotassiumpyrophosphate:tetrasodium pyrophosphate. "SD" means Standard Deviation.Mean Calculus/Rat is based on 12 rats per group. Significance at 95%level.

                  TABLE 2                                                         ______________________________________                                                             Mean            %                                                    Pyro:    Calculus/       Reduction                                Test Solution                                                                             Gantrez  Rat       ∓SD                                                                              from Water                               ______________________________________                                        Water Control                                                                             --       78.25     19.78 --                                       3.3% Pyro, 1.0%                                                                           3.3:1    48.66     16.68 -37.81                                   Gantrez, 0.24% NaF                                                            (Positive Control)                                                            2.3% Pyro, 1.5%                                                                           1.5:1    53.91     22.71 -31.10                                   Gantrez, 0.24% NaF                                                            1.5% Pyro, 1.5%                                                                           1:1      55.33     17.41 -29.29                                   Gantrez, 0.24% NaF                                                            pH 7.0                                                                        ______________________________________                                         1. Briner, M.W. and Francis, M.D. "In vitro and in vivo evaluation of         anticalculus agents." Calcified Tissue Research 11:1022 (1973).          

TABLE 2 shows that compared to the placebo (water control), all testsolutions containing pyrophosphate ion, Gantrez copolymer and sodiumfluoride significantly reduced the incidence of calculus, and all testedpyro:Gantrez ratio produced substantially equal and acceptableanticalculus results.

The following examples illustrate preferred compositions embodying theteachings of this invention.

EXAMPLE 3 DENTIFRICE COMPOSITION

    ______________________________________                                         Ingredient            Parts                                                  ______________________________________                                        Sorbitol (70% solution)                                                                              30.000                                                 Deionized water        25.047                                                 Zeodent 113 (silicon dioxide)                                                                        20.000                                                 Glycerine              10.000                                                 PEG 600 (polyethylene glycol)                                                                        3.000                                                  Sylox 15 (synthetic silica)                                                                          3.000                                                  Tetrasodium pyrophosphate (TSPP)                                                                     2.000*                                                 Gantrez (S-97 Pharmaceutical grade)                                                                  1.500                                                  Sodium lauryl sulfate  1.200                                                  Sodium hydroxide (50% solution)                                                                      1.000                                                  Flavor                 0.950                                                  Iota carrageenan       0.750                                                  Titanium dioxide       0.500                                                  Sodium saccharin       0.300                                                  Sodium fluoride        0.243                                                  ______________________________________                                         *provides 1.3 parts pyrophosphate ion.                                   

EXAMPLE 4 MOUTHWASH

    ______________________________________                                                          Parts                                                       ______________________________________                                        TSPP               1.6*                                                       Ethyl Alcohol      15.0                                                       Gantrez S-97       1.0                                                        Glycerol           10.0                                                       Flavor             0.4                                                        Sodium Saccharin   0.03                                                       NaF                0.05                                                       Pluronic F 108**   2.0                                                        Deionized Water to Q.S.                                                                          100                                                        ______________________________________                                         *provides 1.04 parts pyrophosphate ion                                        **Polyoxyethylenated polyoxypropylene nonioncc block polymer surfactant  

EXAMPLE 5 LOZENGES

    ______________________________________                                                       PARTS                                                          ______________________________________                                        Sugar           75-98                                                         Corn syrup       1-20                                                         Flavor oil      0.1-1.0                                                       Tablet lubricant                                                                              0.1-5                                                         TSPP            0.1-5                                                         Gantrez S-97    0.3-17                                                        NaF             0.005-0.1                                                     Water           0.01-0.2                                                      ______________________________________                                    

EXAMPLE 6 CHEWING GUM

    ______________________________________                                                         Parts                                                        ______________________________________                                        Gum base          10 to 50                                                    Binder             3 to 10                                                    Filler             5 to 80                                                    (sorbitol, mannitol or                                                        combination thereof)                                                          Artificial sweetener                                                                            0.1 to 5                                                    TSPP              0.1 to 5                                                    Gantrez S-97      0.3 to 17                                                   NaF               0.005-0.1                                                   Flavor            0.1 to 5                                                    ______________________________________                                    

This invention has been described with respect to certain preferredembodiments and it will be understood that modifications and variationsthereof obvious to those skilled in the art are to be included withinthe purview of this application and the scope of the appended claims.

We claim:
 1. In an anticalculus oral composition containing in an orallyacceptable vehicle one or a mixture of water soluble linear molecularlydehydrated alkali metal or ammonium polyphosphate salts as essentialanticalculus agent, an amount of a fluoride ion source sufficient tosupply about 25 ppm to about 2,000 ppm of fluoride ions, and one or amixture of water soluble alkali metal or ammonium synthetic anionicpolymeric polycarboxylate salts, the improvement comprising employing insaid composition a polyphosphate ion:polycarboxylate salt weight ratioranging from about 0.3:1 to about 2.5:1.
 2. A composition according toclaim 1 wherein said fluoride ion source comprises sodium fluoride.
 3. Acomposition according to any one of claims 1 or 2 wherein said polymericpolycarboxylate has a molecular weight of about 1,000 to about1,000,000.
 4. A composition according to any one of claims 1, 2 or 3wherein said polymeric polycarboxylate comprises a carboxyvinyl polymer.5. A composition according to any one of claims 1, 2 or 3 wherein saidpolymeric polycarboxylate comprises a copolymer of vinyl methyl etherand maleic acid or anhydride.
 6. A composition according to claim 5wherein said copolymer has a molecular weight of about 30,000 to500,000.
 7. A composition according to claim 5 wherein said copolymerhas a molecular weight of about 70,000.
 8. A composition accordng to anyone of claims 1 to 7 containing about 0.1 to about 7 wt. percent of saidpolyphosphate salt or mixture thereof.
 9. A composition according to anyone of claims 1 to 8 wherein said polyphosphate salt comprises apyrophosphate.
 10. A composition according to claim 9 wherein saidpyrophosphate comprises tetrasodium pyrophosphate.
 11. A compositionaccording to any one of claims 9 or 10 containing about 0.1 to below 3%of pyrophosphate ion.
 12. A composition according to any one of claims 9or 10 containing about 0.1 to 1.3% of pyrophosphate ion.
 13. Acomposition according to any one of claims 1 to 12 wherein the weightratio of polyphosphate ion:polycarboxylate salt ranges from about 0.8:1to about 1.2:1.
 14. A composition according to any one of claims 1 to 13in the form of a toothpaste or gel further containing a dentallyacceptable polishing agent and a gelling agent.
 15. A compositionaccording to any one of claims 1 to 13 in the form of a mouthwashcontaining an aqueous alcoholic vehicle.
 16. A composition accordng toany one of claims 1 to 13 in the form of a lozenge.
 17. A compositionaccording to any one of claims 1 to 13 in the form of chewing gum.
 18. Acomposition according to any one of claims 1 to 17 having a pH of about4.5 to about
 10. 19. A method of inhibiting dental calculus comprisingapplying to dental surfaces in the oral cavity a calculus-inhibitingamount of a composition as defined in any one of claims 1-18.